Staphylococcus aureus CC398: Host Adaptation and Emergence of Methicillin Resistance in Livestock
Lance B. PriceMarc SteggerHenrik HasmanMaliha AzizJesper LarsenPaal Skytt AndersenTalima PearsonAndrew E. WatersJeffrey T. FosterJames M. SchuppJohn D. GilleceElizabeth M. DriebeCindy M. LiuBurkhard SpringerIrena ZdovcAntonio BattistiAlessia FrancoJ. ŻmudzkiŠtefan SchwarzPatrick ButayeÉric JouyConstança PombaM. Concepción PorreroRaymond RuimyTara C. SmithD. Ashley RobinsonJ. Scott WeeseCarmen Sofia ArriolaFangyou YuFrédéric LaurentPaul KeimRobert SkovFrank M. Aarestrup
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Since its discovery in the early 2000s, methicillin-resistant Staphylococcus aureus (MRSA) clonal complex 398 (CC398) has become a rapidly emerging cause of human infections, most often associated with livestock exposure. We applied whole-genome sequence typing to characterize a diverse collection of CC398 isolates (n = 89), including MRSA and methicillin-susceptible S. aureus (MSSA) from animals and humans spanning 19 countries and four continents. We identified 4,238 single nucleotide polymorphisms (SNPs) among the 89 core genomes. Minimal homoplasy (consistency index = 0.9591) was detected among parsimony-informative SNPs, allowing for the generation of a highly accurate phylogenetic reconstruction of the CC398 clonal lineage. Phylogenetic analyses revealed that MSSA from humans formed the most ancestral clades. The most derived lineages were composed predominantly of livestock-associated MRSA possessing three different staphylococcal cassette chromosome mec element (SCCmec) types (IV, V, and VII-like) including nine subtypes. The human-associated isolates from the basal clades carried phages encoding human innate immune modulators that were largely missing among the livestock-associated isolates. Our results strongly suggest that livestock-associated MRSA CC398 originated in humans as MSSA. The lineage appears to have undergone a rapid radiation in conjunction with the jump from humans to livestock, where it subsequently acquired tetracycline and methicillin resistance. Further analyses are required to estimate the number of independent genetic events leading to the methicillin-resistant sublineages, but the diversity of SCCmec subtypes is suggestive of strong and diverse antimicrobial selection associated with food animal production.Modern food animal production is characterized by densely concentrated animals and routine antibiotic use, which may facilitate the emergence of novel antibiotic-resistant zoonotic pathogens. Our findings strongly support the idea that livestock-associated MRSA CC398 originated as MSSA in humans. The jump of CC398 from humans to livestock was accompanied by the loss of phage-carried human virulence genes, which likely attenuated its zoonotic potential, but it was also accompanied by the acquisition of tetracycline and methicillin resistance. Our findings exemplify a bidirectional zoonotic exchange and underscore the potential public health risks of widespread antibiotic use in food animal production.Keywords:
Host adaptation
Multilocus sequence typing
Lineage (genetic)
SCCmec
Surveillance of hospital-acquired methicillin-resistant Staphylococcus aureus (HA-MRSA) infections has shown the emergence and spread of several epidemic MRSA clones over the past 10 years in Belgium. Whether these clones have been imported from abroad or else have arisen locally via staphylococcal cassette chromosome mec (SCCmec) acquisition by successful methicillin-susceptible S. aureus (MSSA) clones is unknown.We determined by PFGE, spa typing, multi-locus sequence typing (MLST) and agr group analysis the genetic relatedness of 103 MSSA and 511 MRSA strains from a national survey of patients admitted to 112 Belgian hospitals in 2003.The 103 MSSA strains presented very diverse genetic backgrounds, they were distributed into 40 distinct PFGE types and clustered in 15 distinct MLST CCs. Up to 45% harboured the same genotype as five major epidemic HA-MRSA clones. These MRSA clones all harbour a type IV SCCmec element.These findings are consistent with multiple recent acquisitions of the more mobile type IV SCCmec by MSSA and suggest that certain genetic backgrounds are conferring a selective advantage, regardless of the resistance profile. However, since the predominant MSSA and MRSA lineages identified in Belgium are disseminated worldwide, importation of epidemic MRSA strains remains an alternative hypothesis.
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Meticillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen in Pakistan and is emerging in the community. This is one of the first reports of the prevalent genotypes of MRSA in both hospital and community settings in Pakistan. Isolates collected in 2006-2007 were characterized by PFGE, staphylococcal cassette chromosome mec (SCCmec) typing and multilocus sequence typing (MLST). PFGE identified nine pulsotypes, the majority of isolates belonging to pulsotypes A (n=70) and B (n=38), which were predominant among hospital-onset MRSA (HO-MRSA) and community-onset MRSA (CO-MRSA) isolates, respectively. Among the HO-MRSA isolates, variants of SCCmec type III were prevalent, whilst SCCmec type IV or variants were predominant in the CO-MRSA isolates. MLST identified two principal sequence types, ST8 and ST239. An association was observed between ST8, PFGE pulsotype B and SCCmec type IV in the CO-MRSA (ST8-MRSA-IV). Similarly, ST239, PFGE pulsotype A and SCCmec type III were associated with HO-MRSA (ST239-MRSA-III). Therefore, the prevalent genotypes circulating in Pakistan at the time of study were ST8-MRSA-IV and ST239-MRSA-III in the community and hospital settings, respectively. A set of HO-MRSA isolates collected in 1997 were characterized by PFGE and SCCmec typing for comparison. The isolates belonged to two PFGE pulsotypes (A, n=28; B, n=11) and contained just two SCCmec types. These results suggest that an increase in genetic diversity occurred over the period 1997-2007 as a result of either microevolution or the importation of strains from surrounding areas.
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Objective:To study the origin and genetic backgrounds of4clinical isolates of Staphylococcus aureus by methods of molecule evolution science and information science.Methods:MIC was estimated by trace broth dilution method.MecA gene was amplified by PCR.MRSA and MSSA were recognized by PBP2a plate latex agglutination.Multilocus Sequencing Typing(MLST)was used to type and analyze the background of4Staphylococcus aureus clinical isolates.Results:SA76,SA137clinical isolates were identified as methicillin-resistant Staphylococcus aureus(MRSA),and SA11and SA155as methicillin-sensible Staphylococcus aureus(MSSA)by antibiotics sensitivity test and mecA gene amplification,as well as detection of PBP2a.SA76and SA137had the same allelic profiles(2-3-1-1-4-4-3)which belonged to ST9,while SA11(1-1-1-1-1-1-1)belonged to ST1and SA155(5-4-1-4-4-6-3)belonged to ST7.Conclusions:MLST is a highly discriminatory method which is easy to standardize.The result is accurate.MRSA clone isolates,MLST typing,genetic background and SCCmec can be correlated.MLST is suitable to molecular evolution research.
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Staphylococcus aureus (S. aureus) bacteremia is one of the most frequent and severe bacterial infections worldwide. Methicillin-resistant Staphylococcus aureus (MRSA) is a serious human pathogen that can cause a wide variety of infections. Comparative genetic analyses have shown that despite the existence of a vast number of genotypes, genotypes are restricted to certain geographical locations. By comparing multilocus sequence typing (MLST) and SCCmec types from 1994 to 2020, the present study intended to discover which genotype genes were related to MRSA infections. MLST, Staphylococcus aureus protein A (spa), and SCCmec typings were performed to determine their relationship during those years. Results revealed that MRSA isolates in the Republic of Korea were distributed among all major staphylococcal cassette chromosome mec (SCCmec) types. The majority of SCCmec isolates belonged to SCCmec type II and type IV. The majority of MLST had the sequence type (ST) 72, 239, 8, or 188. By contrast, minorities belonged to ST22 (SCCmec IV), ST772 (SCCmec V), and ST672 (SCCmec V) genotypes. The SCCmec type was determined for various types. The spa type was dispersed, seemingly regardless of its multidrug resistance property. The MLST type was found to be similar to the existing typical type. These results showed some correlations between resistance characteristics and types according to the characteristics of the MLST types distributed, compared to previous papers. Reports on genotype distribution of MLST and SCCmec types in MRSA are rare. These results show a clear distribution of MLST and SCCmec types of MRSA from 1994 to 2020 in the Republic of Korea.
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ABSTRACT To investigate the evolutionary pattern and genotypic characteristics of methicillin-resistant Staphylococcus aureus (MRSA) strains in the Asian region, 74 MRSA strains isolated from 12 Asian countries were analyzed by multilocus sequence typing (MLST) and SCC mec typing. Overall, a total of 16 genotypes based on sequence type and SCC mec types were identified among MRSA strains from Asian countries. Data revealed two major genotypes of MRSA strains in Asia, with unique geographic distributions. By MLST analysis, all strains from Korea and Japan except one belonged to clonal complex 5 (CC5) while most MRSA isolates from other Asian countries belonged to CC239. SCC mec typing showed that most isolates from Korea and Japan were SS mec type II whereas SCC mec type III (or IIIA) was the most common type in strains from other Asian countries. Our data documented a unique geographic distribution and evolutionary pattern of MRSA clones in Asia.
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ABSTRACT Molecular methods for the rapid identification of methicillin-resistant Staphylococcus aureus (MRSA) are generally based on the detection of an S. aureus -specific gene target and the mecA gene. However, such methods cannot be applied for the direct detection of MRSA from nonsterile specimens such as nasal samples without the previous isolation, capture, or enrichment of MRSA because these samples often contain both coagulase-negative staphylococci (CoNS) and S. aureus , either of which can carry mecA. In this study, we describe a real-time multiplex PCR assay which allows the detection of MRSA directly from clinical specimens containing a mixture of staphylococci in <1 h. Five primers specific to the different staphylococcal cassette chromosome mec (SCC mec ) right extremity sequences, including three new sequences, were used in combination with a primer and three molecular beacon probes specific to the S. aureus chromosomal orfX gene sequences located to the right of the SCC mec integration site. Of the 1,657 MRSA isolates tested, 1,636 (98.7%) were detected with the PCR assay, whereas 26 of 569 (4.6%) methicillin-susceptible S. aureus (MSSA) strains were misidentified as MRSA. None of the 62 nonstaphylococcal bacterial species or the 212 methicillin-resistant or 74 methicillin-susceptible CoNS strains (MRCoNS and MSCoNS, respectively) were detected by the assay. The amplification of MRSA was not inhibited in the presence of high copy numbers of MSSA, MRCoNS, or MSCoNS. The analytical sensitivity of the PCR assay, as evaluated with MRSA-negative nasal specimens containing a mixture of MSSA, MRCoNS, and MSCoNS spiked with MRSA, was ∼25 CFU per nasal sample. This real-time PCR assay represents a rapid and powerful method which can be used for the detection of MRSA directly from specimens containing a mixture of staphylococci.
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To investigate the source and genetic background of methicillin-resistant Staphylococcus aureus in the year of 2006, in China.From January to December 2006, a total number of 302 consecutive and non-repetitive methicillin-resistant Staphylococcus aureus were collected from 17 Teaching hospitals in 15 areas. Genotypes of SCCmec were determined by multiplex PCR and multilocus sequence typing (MLST) was used to type the house-keeping genes. The implementation of the spa typing method was straightforward, and the results obtained were reproducible, unambiguous, and easily interpreted.All areas but Dalian harbored SCCmec III while Dalian harbored SCCmec II most. There were two strains in Guangzhou, harboring SCCmec IV. There were four strains of sequence type (ST), with ST239 accounted for 46.7% and ST5 accounted for 44.4%. ST59 accounted for 6.7% and ST88 accounted for 2.2%. There were fourteen strains of Spa typing, with t30 accounted for 52.6%; t37 accounted for 27.2%; t2 accounted for 12.9%; t632 accounted for 2.3%; t437 accounted for 1.3%; t570, t601 accounted for 0.7%; t377, t459, t796, t899, t1152, t2649 accounted for 0.3%; no-typing accounted for 0.3%, respectively. pvl gene was not detected.The main clone strains were ST239-MRSA-SCCmec III-t30, ST5-MRSA-SCCmec II-t2, with unique geographic distributions across the whole nation.
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Objectives: To identify the staphylococcal cassette chromosome mec (SCCmec) types of methicillin-resistant Staphylococcus aureus (MRSA) isolated from bovine milk, and examine the genetic relatedness between MRSA from bovine milk and MRSA from human isolates.
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ABSTRACT A protocol for multilocus sequence typing (MLST) of methicillin-resistant Staphylococcus aureus (MRSA) was adapted to real-time LightCycler System PCR for efficient and rapid amplification of seven housekeeping genes in the same PCR run and real-time detection of the products. The method was evaluated on a representative and well-characterized collection of clinical MRSA isolates ( n = 57) obtained from an area of low endemicity. Twenty sequence types (STs) and nine clonal complexes were identified. Combining STs and the staphylococcal cassette chromosome mec (SCC mec ) type identified 27 different genotypes, and type IV SCC mec was present in 11 different STs. The presence of the Panton Valentine leukocidin (PVL) genes was found in isolates of four different STs. Eleven different STs were found among the community-acquired as well as among the hospital-acquired MRSA. The genetic heterogeneity was also denoted by pulsed-field gel electrophoresis analysis that showed 24 different pulsotypes among the 57 MRSA isolates. The presence of more than one different type of SCC mec in the same ST indicates that the MRSA clones have arisen at several occasions in the same genetic background by independent acquisition of SCC mec into methicillin-sensitive strains. This circumstance shows the importance of combining MLST data with SCC mec -typing results when investigating the origins of MRSA.
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